Article
Cell Biology
Lais da Silva, Jinmai Jiang, Corey Perkins, Kalina Rosenova Atanasova, Julie K. Bray, Gamze Bulut, Ana Azevedo-Pouly, Martha Campbell-Thompson, Xiaozhi Yang, Hesamedin Hakimjavadi, Srikar Chamala, Ranjala Ratnayake, Raad Z. Gharaibeh, Chenglong Li, Hendrik Luesch, Thomas D. Schmittgen
Summary: Pancreatic acinar cells can dedifferentiate into ductal-like progenitor cells through a process called acinar ductal metaplasia (ADM), and maintaining the acinar cell phenotype suppresses tumor formation. A novel pStat3 inhibitor and histone deacetylase inhibitor were found to inhibit ADM and reverse ADM, providing a potential therapeutic strategy for blocking aberrant ductal reprogramming of acinar cells.
CELL DEATH DISCOVERY
(2022)
Article
Cell & Tissue Engineering
Ling Huang, Ridhdhi Desai, Daniel N. Conrad, Nayara C. Leite, Dipikaa Akshinthala, Christine Maria Lim, Raul Gonzalez, Lakshmi B. Muthuswamy, Zev Gartner, Senthil K. Muthuswamy
Summary: Induction of human pluripotent stem cells towards pancreatic ductal and acinar organoids has provided a renewable source for modeling exocrine development and diseases. The study demonstrated the lineage tropism and plasticity for oncogene action in the human pancreas, with specific oncogenes like GNAS(R201C) and KRAS(G12D) showing differential effects on ductal and acinar organoids both in culture and in vivo.
Review
Biochemistry & Molecular Biology
Louis Marstrand-Dauce, Diane Lorenzo, Anais Chassac, Pascal Nicole, Anne Couvelard, Cecile Haumaitre
Summary: Adult pancreatic acinar cells can undergo pancreatic acinar-to-ductal metaplasia (ADM), where differentiated acinar cells transform into duct-like cells. This process can lead to the development of pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic ductal adenocarcinoma (PDAC). Factors such as obesity, chronic inflammation, and genetic mutations contribute to the development of ADM and PanIN. Understanding the cellular and molecular mechanisms of ADM is crucial for developing new therapeutic strategies for pancreatitis and PDAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Wenjie Ge, Algera Goga, Yuliang He, Pamuditha N. Silva, Christian Kurt Hirt, Karolin Herrmanns, Ilaria Guccini, Svenja Godbersen, Gerald Schwank, Markus Stoffel
Summary: miR-802 is a highly abundant and acinar-enriched pancreatic miRNA that is silenced during early stages of injury or oncogenic Kras(G12D)-induced transformation. Genetic ablation of mir-802 cooperates with Kras(G12D) by promoting ADM formation. miR-802 deficiency results in de-repression of the miR-802 targets Arhgef12, RhoA, and Sdc4, activation of RhoA, and induction of the downstream RhoA effectors ROCK1, LIMK1, COFILIN1, and EZRIN, thereby increasing F-actin rearrangement.
Article
Multidisciplinary Sciences
Patrick Neuhofer, Caitlin M. Roake, Stewart J. Kim, Ryan J. Lu, Robert B. West, Gregory W. Charville, Steven E. Artandi
Summary: Studies have identified a rare TERT-positive subpopulation of acinar cells in the pancreas that play a role in pancreatic renewal and potential initiation of PDAC. Expression of mutant Kras in these TERT-high acinar cells accelerates acinar clone formation and transdifferentiation, highlighting their potential role in pancreatic tumorigenesis as early cancer precursor lesions.
Review
Cell Biology
Kailing Yang, Xiaojia Li, Keping Xie
Summary: Tumorigenesis and senescence, although seemingly contradictory, share similar mechanisms. Pancreatic ductal adenocarcinoma (PDA) is a lethal disease that progresses through multiple steps. Senescence is prevalent in PDA development, but also plays a significant role in promoting tumorigenesis. This review focuses on the dual roles of senescence in PDA, the signaling effectors that regulate senescence, and molecular targets for controlling senescence in PDA treatment.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Hwanik Kim, Jung Kwon Kim, Gheeyoung Choe, Sung Kyu Hong
Summary: ASAP is found in approximately 5% of prostate biopsies, with 30-40% of patients subsequently being diagnosed with prostate cancer within 5 years. This study suggests the importance of immediate repeat biopsy after an ASAP diagnosis, as 45.1% of patients were later found to have prostate cancer, with 19.6% having clinically significant disease.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Hong Hua Yan, Kyung Hee Jung, Ji Eun Lee, Mi Kwon Son, Zhenghuan Fang, Jung Hee Park, Soo Jung Kim, Ju Young Kim, Ju Han Lim, Soon-Sun Hong
Summary: The study revealed that ANGPTL4 plays a critical role in KRAS(G12D)-induced ADM, promoting its progression and influencing PDAC development by regulating periostin. The ANGPTL4/periostin axis is considered a potential therapeutic target for ADM-derived PDAC.
Article
Medicine, Research & Experimental
Nikita Bhalerao, Asmi Chakraborty, Michael P. Marciel, Jihye Hwang, Colleen M. Britain, Austin D. Silva, Isam E. Eltoum, Robert B. Jones, Katie L. Alexander, Lesley E. Smythies, Phillip D. Smith, David K. Crossman, Michael R. Crowley, Boyoung Shin, Laurie E. Harrington, Zhaoqi Yan, Maigen M. Bethea, Chad S. Hunter, Christopher A. Klug, Donald J. Buchsbaum, Susan L. Bellis
Summary: This study investigates the role of aberrant glycosylation, specifically the upregulation of ST6 beta-galactoside alpha 2,6 sialyltransferase 1 (ST6GAL1), in pancreatic ductal adenocarcinoma (PDAC). The findings reveal that ST6GAL1 is upregulated in both early-stage and advanced PDAC, and its tumor-promoting function is elucidated through tumor xenograft experiments and a genetically engineered mouse model. Additionally, the study highlights ST6GAL1's involvement in acinar to ductal metaplasia (ADM) and its role in activating EGFR to promote this process.
Review
Biochemistry & Molecular Biology
Seema Parte, Rama Krishna Nimmakayala, Surinder K. Batra, Moorthy P. Ponnusamy
Summary: Pancreatic cancer is a deadly neoplastic malignancy with high mortality rates. Acinar to ductal cell metaplasia plays a crucial role in tumor initiation, making it important for understanding the pathogenesis and early diagnosis of pancreatic cancer.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Pathology
Koushik K. Das, Jeffrey W. Brown, Carlos Fernandez del-Castillo, Tiffany Huynh, Jason C. Mills, Yoko Matsuda, Kiron M. Das, Mari Mino-Kenudson
Summary: mAb Das-1 shows high specificity in distinguishing high-grade PanIN/PDAC from low-grade PanIN lesions, which may be helpful for pre-operative diagnosis and clinical risk stratification of PDAC.
Article
Multidisciplinary Sciences
Kohei Yamakawa, Noriko Inomata, Atsuhiro Masuda, Mamoru Takenaka, Hirochika Toyama, Keitaro Sofue, Arata Sakai, Takashi Kobayashi, Takeshi Tanaka, Masahiro Tsujimae, Shigeto Ashina, Masanori Gonda, Shohei Abe, Shigeto Masuda, Hisahiro Uemura, Shinya Kohashi, Kae Nagao, Yoshiyuki Harada, Mika Miki, Yosuke Irie, Noriko Juri, Hideyuki Shiomi, Maki Kanzawa, Tomoo Itoh, Takumi Fukumoto, Yuzo Kodama
Summary: Pancreatic cancer primarily arises from precancerous lesions such as PanIN and ADM. This study aimed to investigate the relationship between EUS findings and these lesions. The results showed that abnormal EUS findings were significantly associated with a higher frequency of PanIN and ADM, and lobularity may be a predictor of increased precancerous lesions.
SCIENTIFIC REPORTS
(2023)
Article
Gastroenterology & Hepatology
Andrea Costamagna, Dora Natalini, Maria del Pilar Camacho Leal, Matilde Simoni, Luca Gozzelino, Paola Cappello, Francesco Novelli, Chiara Ambrogio, Paola Defilippi, Emilia Turco, Elisa Giovannetti, Emilio Hirsch, Sara Cabodi, Miriam Martini
Summary: High expression of p130Cas is associated with higher histologic grade and poor prognosis in PDAC. Deletion of p130Cas inhibits acinar-derived tumorigenesis and progression by suppressing PI3K-AKT signaling. Targeting the PI3K pathway may be a rational therapeutic strategy for tumors with high expression of p130Cas.
Review
Gastroenterology & Hepatology
Adrien Grimont, Steven D. Leach, Rohit Chandwani
Summary: The pancreas contains a high level of cellular plasticity, which can alter cellular identity during injury, regeneration, and repair processes. The cell of origin of pancreatic cancer is difficult to determine, but research suggests that acinar cells may be the most likely origin of intraductal papillary neoplasms and pancreatic intraepithelial neoplasia, while both acinar and ductal cells can undergo malignant transformation into pancreatic ductal adenocarcinoma.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Cell Biology
Sen Yang, Qiaofei Liu, Quan Liao
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that can only be cured by surgery in its early stages, but recurrence remains a high possibility. Tumor-associated macrophages (TAMs) play a crucial role in PDAC development, promoting tumor behaviors such as tumorigenesis and metastasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
